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 22 May 2018

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News

Transglutaminase type II role in celiac disease pathogenesis

Data in November's issue of Gastroenteorlogy indicates a novel and unexpected biological role for surface transglutaminase type II in the pathogenesis of celiac disease.

News image

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In celiac disease, transglutaminase type II has 2 fundamental roles.

Firstly, it is the autoantigen recognized by highly specific autoantibodies and secondly, it is the modifier of pathogenic gliadin T-cell epitopes.

It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin.

Dr Londei and colleagues studied the validity of this strategy using the organ culture approach.

Duodenal biopsy specimens from

The researchers included 30 treated patients with celiac disease, 33 untreated patients with celiac disease, and 24 controls.

Surface transglutaminase type II contained gliadin-specific T-cell activation
Gastroenterology

Duodenal biopsy specimens were cultured with or without gliadin peptides p31 to 43, pα-9, and deamidated pα-9 for 20 minutes, 3 hours, and 24 hours.

Transglutaminase type II inhibitor R283 or anti- transglutaminase CUB 7402 or anti-surface transglutaminase type II mAbs were used in cultures of 47 subjects.

T84 cells were also cultured with or without peptides with or without transglutaminase type II inhibitors.

The researchers assessed mucosal modifications after culture by immunofluorescence, or in situ detection of transglutaminase activity.

The team also evaluated mucosal modifications by confocal microscopy, and fluorescence-activated cell sorter analysis.

The researchers found that the enzymatic inhibition of transglutaminase type II only controlled gliadin-specific T-cell activation.

The binding of surface transglutaminase type II contained gliadin-specific T-cell activation and p31 to 43 induced actin rearrangement.

In addition, the team noted that actin rearrangement was induced by epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells.

Dr Londei's team commented, “These data indicate a novel and unexpected biological role for surface transglutaminase type II in the pathogenesis of celiac disease.”

“These findings suggest a third role for transglutaminase type II in celiac disease.”

“These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of transglutaminase type II with possible repercussions in other diseases.”

Gastroenterol 2005: 129(5): 1400-13
18 November 2005

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